New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O...
Transcript of New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O...
![Page 1: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/1.jpg)
BONE METABOLISM
NURINA TYAGITABIOCHEMISTRY DEPARTMENT
MEDICINE FACULTY OF UNISSULA
![Page 2: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/2.jpg)
LEARNING OUTCOME• BONE OVERVIEW• MINERALISASI TULANG• ALKALI PHOSPHATASE• VITAMIN D• CALCIUM
![Page 3: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/3.jpg)
BONE OVERVIEW BONE COMPOSITION REMODELLING CYCLE
BONE’S CELLS
![Page 4: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/4.jpg)
BONE COMPOSITIONPENYUSUN:ORGANIK (KOMPONEN PROTEIN)90-95 % Kolagen tipe I5-10% Kolagen tipe V & protein non kolagen
INORGANIK (KOMPONEN MINERAL):Terutama adalah crystalline hydroxyapatite (Ca10(PO4)6(OH)2)Dan sodium, magnesium, karbonat, Fluoride99% kalsium tubuh berada di TULANGHidroksiapatit berguna untuk bone strength & resilience
![Page 5: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/5.jpg)
TULANG merupakan struktur dinamis yang secara kontinyumengalami siklus REMODELLINGTujuan REMODELLING : tulang dapat beradaptasi thd perubahan(misal: kenaikan BB, pengaruh hormon)
Siklus REMODELLING ini t.d:RESORPSI penyerapan kembali mineral yg diperlukan tubuh
dilakukan oleh sel OSTEOKLASDEPOSISI penumpukan mineral dalam tulang
Dilakukan oleh sel OSTEOBLAS
REMODELLING CYCLE
![Page 6: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/6.jpg)
OSTEOSIT
Berasal dari osteoblas Ditemukan di tulang
matur Terlibat dalam
pemeliharaan matrikstulang
Usianya sangat panjang,average half life: 25 years
BONE’S CELLS
![Page 7: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/7.jpg)
RUFFLED BORDER: Berperandlm resorpsi tulang
Enzim ATPase mengeluarkan proton melintasi ruffled border arearesorpsi semakin me↓kan pH microenvironment (pH menjadi ≤4) ↑solubilitas hidroksiapatit Ca2+, H3PO4, H2CO3, & air demineralisasi
OSTEOKLAS
Lysosomal acid protease (mis. Katepsin) released cerna matriksprotein tulang transfer ke kapiler
![Page 8: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/8.jpg)
OSTEOBLAST
Sel mononuklear berasal dariprekursor mesenkimal pluripoten
Fungsi:• Sintesis protein tulang • Sintesis berbagai Growth factor &sitokin2
• Bertanggung jawab deposisi matrikstulang baru (osteoid) &mineralisasinya
Osteoblast mengendalikan mineralisasi melalui pengaturanpassage ion kalsium & fosfat yang melintasi membranpermukaan osteoblast
![Page 9: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/9.jpg)
MINERALISASI TULANG MINERALISASI PENGATURAN FUNGSI OSTEOBLAS
& OSTEOKLAS
![Page 10: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/10.jpg)
1. Pembentukan kristal hidroksiapatit dalam vesikel matriks yangbertunas dari permukaan membran kondrosit, osteoblas, &odontoblast
2. Propagasi hidroksiapatit ke matriks ekstraselular & deposisidiantara fibril kolagen
3. Penghambatan pembentukan hidroksiapatit oleh pirofosfatinorganik ekstraselular
4. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolisapirofosfat sediakan fosfat inorganik u/ mineralisasi
MINERALISASI
![Page 11: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/11.jpg)
Regulation of osteoBlastsfunction
• Stimulation• PTH (fast reaction - activation of calcium pump ? – pumping Ca to
ECF)
• 1,25 Dihydrocholecalciferol
• IL-1
• T3, T4
• hGH, IGF-1 (insuline-like growth factor)
• PGE2 (prostaglandine)
• TNF (tumor necrosis factor)
• Estrogens ?
• Inhibition• Corticosteroids
![Page 12: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/12.jpg)
Regulation of osteoClastsfunction
• Stimulation• PTH (not directly – through stimulation of osteoblasts)• 1,25 Dihydrocholecalciferol (not directly – through
stimulation of osteoblasts)• IL-6, IL-11
• Inhibition• Calcitonin (directly – receptors)• Estrogens (by inhibiting production of certain
cytokines)• TGF-β (transforming growth factor)• PGE2(prostaglandine)
![Page 13: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/13.jpg)
Merupakan enzim glikoprotein yangterdapat di membran sel osteoblast,
termasuk Famili enzim zincmetalloprotein.
Fungsi: memisahkan gugus fosfatterminal dari ester fosfat organikBone alkaline phosphatase (BAP):
bone-specific isoform of alkalinephosphatase
BAP reflects the biosynthetic activityof these bone-forming cells.
BAP has been shown to be asensitive and reliable indicator of bone
metabolism.
ALKALI FOSFATASE
![Page 14: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/14.jpg)
PENINGKATAN BAP :Jika Aktivitas osteoblastik ↑Misal:Paget diseaseOsteomalasia
BAP TUMOR MARKER Osteogenic sarcoma Metastasis tulang Leukemia Myelofibrosis Myeloma tumor marker Hyperthyroidism
Secara fisiologis ↑ : Pertumbuhan anak Orang dewasa > 50 tahun Bone growth Healing fracture Akromegali
![Page 15: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/15.jpg)
MALES:<2 years: 25-221 mcg/L2-9 years: 27-148 mcg/L10-13 years: 35-169 mcg/L14-17 years: 13-111 mcg/LAdults: < or =20 mcg/L
FEMALES<2 years: 28-187 mcg/L2-9 years: 31-152 mcg/L10-13 years: 29-177 mcg/L14-17 years: 7-41 mcg/LAdultsPremenopausal: < or =14 mcg/LPostmenopausal: < or =22 mcg/L
NILAI NORMAL BAP
![Page 16: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/16.jpg)
VITAMIN D VITAMIN D DALAM TUBUH VIT D DEFICIENCY VIT D TOXICITY
![Page 17: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/17.jpg)
VITAMIN D• Vitamin D is not strictly a vitamin since it
can be synthesized in the skin• Only when sunlight is inadequate is a dietary
source required• The main function : regulation of calcium
absorption and homeostasis
17
![Page 18: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/18.jpg)
18
hidroksilasi
calcidiol
calcitriol
Peran lain calcitriol: Sekresi insulin Sintesis & sekresi
parathyroid & thyroidhormon
Inhibisi produksi IL & Ig Diferensiasi monosit sel
prekursor Modulasi proliferasi sel
![Page 19: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/19.jpg)
19
Vitamin D adl hormon steroid yang mengatur ekspresigen tertentu dan interaksinya dg reseptor intracellular
![Page 20: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/20.jpg)
VIT D DEFICIENCY• Rickets :the bones of children are under mineralized as
a result of poor absorption of calcium• Osteomalacia (in adults ):results from demineralization of bone in
women who have little exposure to sunlight,often after several pregnancies
![Page 21: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/21.jpg)
![Page 22: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/22.jpg)
VIT D TOXICITY• contraction of blood vessels• high blood pressure• calcinosis—the calcification of soft tissues.
FOOD SOURCE :Fortified milk, liver, butter & fatty fish
RDI : 2,5 mg
![Page 23: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/23.jpg)
CALCIUMo FUNGSIo CALCIUM TUBUHo HORMONAL REGULATORSo CALCIUM HOMEOSTASIS
![Page 24: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/24.jpg)
CALCIUM• Mempunyai bermacam2
fungsi, a.l : Pembentukan tulang &
gigi Penjalaran impuls saraf Kontraksi otot Koagulasi darah Signalling intraseluler Sekresi enzim pencernaan Sekresi & kerja hormon
![Page 25: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/25.jpg)
CALCIUMKation EKSTRASELULAR utama pada manusia.95-99% kadar Kalsium tubuh tersimpan di TULANG sebagai
KRISTAL HIDROKSIAPATIT Sisanya tersimpan di CAIRAN EKSTRASELULER dan
exchangeable dengan :• Periosteal fluid• Bone-forming surfaces• Soft tissuesKeseimbangannya tergantung bone FORMATION &RESORPTION (diatur oleh HORMON)
![Page 26: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/26.jpg)
Konsentrasi Kalsium plasma: 8.8-10.3 mg/dL (2.20-2.58mmol/L)Dipelihara oleh: Parathyroid hormone (PTH) Metabolit vit D Kalsitonin Sitokin : TGF-β, IL-6
Target sites :
Absorbsi Reabsorbsi & ekskresi Akresi & mobilisasi
![Page 27: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/27.jpg)
Kalsium tubuh dlm 3 bentuk:1.Non diffusible calcium bound to albumin (45%)2.Diffusible complexes of calsium w/ lactate, bicarbonate, fosfat,
sulfat, sitrat, anion lain (5%)3.Diffusible ionized calcium, Ca2+ (50%) physiological active
form diatur oleh klnj. PARATYROIDKeseimbangan ke-3 bentuk kalsium dipengaruhi oleh pH:pH 6.8 Ca2+ sebesar 54%pH 7.8 Ca2+ sebesar 38%
PHOSPHATE
80% bergabung dengan kalsium kristal HIDROKSIAPATIT diTULANG
![Page 28: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/28.jpg)
Dietary requirements• Dietary requirements:
• Adult : 800 mg/day;• Women during pregnancy, lactation and post-
menopause: 1.5 g/day;• Children (1-18 yrs): 0.8-1.2 g/ day;• Infants: (< 1 year): 300-500 mg /day
• Food Sources:• Best sources: milk and milk product;• Good sources: beans, leafy vegetables, fish,
cabbage, egg yolk.
![Page 29: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/29.jpg)
• Absorption of calcium:• in small intestine (duodenum), first half jejunum
against electrical and concentration gradient, by anenergy dependent active process, which influenced byseveral factors.
MechanismSimple diffusion
An active transport involving Ca pump(Ca2+-ATPase), requiring calcitriol
Uptake by the brush-bordercell membraneDiffusion through cytoplasm
![Page 30: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/30.jpg)
Factor promoting Ca absorption1. Vit.D induce the synthesis of Ca binding protein inthe intestinal epithelial cells and promotes Caabsorption.
2. Parathyroid hormone (PTH) enhances Ca absorptionthrough the increased synthesis of calcitriol.
3. Acidity (low pH) is more favorable for Ca absorption.4. Lactose promotes calcium uptake by intestinal cell.5. Lysine and arginine facilitate Ca absorption.
![Page 31: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/31.jpg)
Factor inhibiting Ca absorption1. Phytates and oxalates form insoluble salts andinterfere with Ca absorption.2. The high content of dietary phosphate results in theformation of insoluble Ca phosphate and prevent Cauptake.
Dietary ratio of Ca : P ---1:1 to 2:1--- is ideal for Caabsorption.
3. The free fatty acids are react with Ca to forminsoluble Ca soaps.4. The alkaline condition (high pH) is unfavorable forCa absorption.5. High content of dietary fiber interferes with Caabsorption.6. Low estrogen levels (postmenopausal women)
![Page 32: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/32.jpg)
intakeexcretion
1000 gCa++stored inbone
Calcium homeostasis
BloodCa++
small intestine
kidney
Ca++lost in urine
Calcium inthe diet
calcium lost in feces
Ca++ absorbedinto blood
calcium resorption
calcium deposition
storagebone
![Page 33: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/33.jpg)
Calcium cycling in bone tissue• Bone formation
• Osteoblasts• Synthesize a collagen matrix that holds
Calcium Phospate in crystallized form• Once surrounded by bone, become
osteocyte
• Bone resorption• Osteoclasts
• Change local pH, causing Ca++ andphosphate to dissolve from crystalsinto extracellular fluids
![Page 34: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/34.jpg)
Hormonal Regulators• Calcitonin (CT)
• Lowers Ca++ in the blood• Inhibits osteoclasts
• Parathormone (PTH)• Increases Ca++ in the blood• Stimulates osteoclasts
• 1,25 Vitamin D3• Increases Ca++ in the blood• Increase Ca++ uptake from the gut• Stimulates osteoclasts
![Page 35: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/35.jpg)
Calcitonin (CT)
• Secreted from the C cellsin the thyroid
• Lowers Ca++ in blood• Promotes deposition of
Ca++ into bone (inhibitsosteoclasts)
• Control of secretion fromc-cells:
CT
![Page 36: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/36.jpg)
Parathormone (PTH)• Increases Ca++ in blood• Increases Ca++ resorption from the bone
• Stimulates osteoclasts• Increases number of osteoclasts
• Increases Ca++ resorption from nephron• Control of secretion:
• Necessary for fine control of Ca++ plasmalevels
![Page 37: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/37.jpg)
1,25 Vitamin D3• Increases Ca++ uptake from the gut
• Increase transcription and translation of Ca++ transport proteins in gut epithelium
• Minor roll: also stimulates osteoclasts• Increase Ca++ resorption from the bone
Cholesterol precursor 7-dehydrocholesterol
UV
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3
Low plasma Ca++ increase kidney enzymes
![Page 38: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/38.jpg)
Calcium homeostasis
BloodCa++
small intestine
kidney
Ca++
Ca++
Ca++
bone 1,25 Vit. D3 (+)
1,25 Vit D3
deposition
Calcitonin (-)
Ca++PTH
Parathormone (+)
resorption
![Page 39: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/39.jpg)
Regulation of Calcium Homeostasis
![Page 40: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/40.jpg)
Defisiensi Calcium• Defisiensi vit D• Hipomagnesemia• Hipolbuminemia• Inadekuat diet• Alkalosis menurunkan serum Ca++ dengan
meningkatkan ikatan Ca dg serum albumin TETANI
![Page 41: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/41.jpg)
Calcium Deficiencies -Rickets
weakness and deformity of the bones that occurs fromvitamin D deficiency or dietary deficiency of Ca and Pin a growing person or animal.
![Page 42: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/42.jpg)
Calcium Deficiencies -Osteoporosis
progressive loss of bone density, thinning of bone tissueand increased vulnerability to fractures in the elderlypeople of both sexes.
![Page 43: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/43.jpg)
Fosfor• ANION INTRASELULER terbanyak• FUNGSI :Counter ion Ca++ dalam mineralisasiTransferable functional group on
nucleotide triphosphateBuffer dalam darah
o DEPLESI : oleh karena ALKALOSIS
![Page 44: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/44.jpg)
Functions of Phosphorus• Essential for the development of bones
and teeth• Phospholipids, Phosphoproteins• Component of:
• DNA & RNA• ATP, NAD+, NADP+
• Energy metabolism: ATP, GTP• Maintenance of blood pH: phosphate
buffer system
![Page 45: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/45.jpg)
Dietary requirements• The recommended dietary allowance (RDA)
of phosphate is based on the intake ofcalcium.• For adult, the ratio of Ca:P of 1:1 is
recommended (800mg/day);• For infant, however, the ratio is around 2:1,
which is ratio found in human milk.• Sources:
• milk, cereals, leafy vegetable, meat, eggs.
![Page 46: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/46.jpg)
Absorption and Excretion
Absorption:Phosphate absorption occur from jejunum1. Calcitriol promotes phosphate uptake along with calcium.2. absorption of P and Ca is optimum when the dietary Ca:P is
1:1-2:1.3. acidity favors while phytate decreases phosphate uptake by
intestinal cells.
Excretion:About 500 mg phosphate is excreted in urine per day. The
reabsorption of phosphate by renal tubules is inhibited by PTH.
![Page 47: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/47.jpg)
• Importance of Ca:P ratio• The ratio of plasma Ca:P is important for calcification of
bones.• The product of Ca×P (in mg/dl) in child is around 50 and
in adults around 40. This product is less than 30 in rickets.
• Phosphorus Deficiency• Rickets, osteomalacia, osteoporosis
![Page 48: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/48.jpg)
hormone
osteolysis
P excretion from kidney
osteogenesis
Ca excretion from kidney
Blood phosphorus
Blood calcium
1,25 DHCC
Ca absorption in intestine
PTH CT
↑↑ ↑ ↓
↑↓
↑
↑
↑
↑
↑
↑ ↑↑ ↓
↓ ↓
↓ ↑
↑
↑↓
↓
Factors Regulating Ca and P
![Page 49: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/49.jpg)
F. Saraç & F. Saygılı (2007) Causes of High Bone AlkalinePhosphatase, Biotechnology & Biotechnological Equipment,21:2, 194-197, DOI:10.1080/13102818.2007.10817444
REFERENCES
![Page 50: New BONE METABOLISM · 2019. 3. 22. · Terutama adalah crystalline hydroxyapatite (Ca1 0(PO 4)6(O H)2) Dan sodium, magnesium, karbonat, Fluoride 99% kalsium tubuh berada di TULANG](https://reader035.fdocuments.net/reader035/viewer/2022081409/60758413040b9467de2fa103/html5/thumbnails/50.jpg)
THANKYOU